The use of bone morphogenetic proteins (BMPs) or other osteoinductive factors in combination with a suitable carrier matrix to promote bone growth and healing at a site in a patient is well known. Reference may be drawn, for example, to U.S. Pat. No. 6,551,995 to Oppermann et al., which is incorporated herein by reference, and to U.S. Pat. No. 6,949,251 to Dalal et al., also incorporated herein by reference.
Briefly, a highly porous, biodegradable carrier matrix is provided, which serves as a scaffolding for the formation of host bone tissue. This matrix is ideally impregnated with one or more osteoinductive factors and/or other bioactive agents. These bioactive agents may include, but are not limited to, antimicrobials, antibiotics, antimyobacterial, antifungals, antivirals, antineoplastic agents, antitumor agents, agents affecting the immune response, blood calcium regulators, agents useful in glucose regulation, anticoagulants, antithrombotics, antihyperlipidemic agents, cardiac drugs, thyromimetic and antithyroid drugs, adrenergics, antihypertensive agents, cholnergics, anticholinergics, antispasmodics, antiulcer agents, skeletal and smooth muscle relaxants, prostaglandins, general inhibitors of the allergic response, antihistamines, local anesthetics, analgesics, narcotic antagonists, antitussives, sedative-hypnotic agents, anticonvulsants, antipsychotics, anti-anxiety agents, antidepressant agents, anorexigenics, non-steroidal anti-inflammatory agents, steroidal anti-inflammatory agents, antioxidants, vaso-active agents, bone-active agents, osteogenic factors, osteoinductive factors, antiarthritics, and diagnostic agents. A preferred embodiment would include recombinant human BMPs (rhBMPs). The biodegradable matrix is then surgically placed at a target site where bone formation is desired, such as a fracture site or a spinal fusion site. The osteoinductive factors act much like a catalyst, encouraging the necessary cells (including, but not limited to, mesenchymal stem cells, osteoblasts, and osteoclasts) to more rapidly migrate into the matrix, which is eventually resorbed via a cell-mediated process and newly formed bone is deposited at the target site. In this manner severe fractures may be healed, and vertebrae successfully fused.
A singular problem is that the osteoinductive factors are often proteins, and hence subject to degradation from acids, enzymes and other compounds that leach both from tissue surrounding the target site and from the bone tissue growing into the carrier matrix. As a result, it is believed that the therapeutic efficacy of the carrier matrix and factors diminishes with time, and also as it is replaced with host tissue and as the osteoinductive factors leach from the carrier matrix. Although this may not be a problem for target sites where relatively fast bone growth is expected, this can become a problem when the bone growth is slow; such slow growth may be exhibited, for example, in closed fractures, and with patients with known co-morbidities, such as smokers, diabetics, and those on steroids.
It is therefore desirable to provide methods and related systems that insure that carrier matrices retain their full efficacy over time to maximally promote bone growth at a target site.